The divergent HIV-1 group O strains (HIV-1/O) are endemic in Cameroon and naturally resistant to NNRTI, largely used as first-line therapy in this country. Alternative therapeutic strategies are thus needed. DynaM-O is a prospective open-label study comparing the immuno-virological response to HAART, including two NRTI and one PI in HIV-1/O and HIV-1 group M (HIV-1/M) infected-naïve patients. Secondary objectives are to compare the kinetic of viral load responses and the CD4 restoration.
HAART was initiated in naïve patients according to the national guidelines; HIV-1/O and HIV-1/M patients were matched on sex, age, CD4, Hb level and HBV status with ratio of 1:2. The primary endpoint was the percentage of patients having an undetectable viral load (VL < 60 cp/mL) at W96. Adherence to treatment was also monitored.
47 Cameroonian patients HIV-1/O and 94 HIV-1/M were included; results were available for 128 patients (13 died or were lost-to follow-up). At baseline, VL was significantly lower (p< 0.0001) in HIV-1/O with a median at 4.3 log cp/mL versus 5.1 in HIV-1/M. Kinetic of VL response was faster for HIV-1/O infected patients until W24. At W96, 95% of HIV-1/O samples were < 60 cp/mL vs 83% of HIV-1/M in per protocol analysis (p=0.09); but no difference was observed at the threshold of 200 cp/mL (97% in both groups). At baseline, median CD4 counts were well balanced between the two groups (227 vs 215, in HIV-1/O and HIV-1/M respectively, p=0.68); at W96, a +50% CD4 gain compared to baseline was observed for 78% vs 89% of the HIV-1/O and HIV-1/M patients respectively (p=0.27), confirming the differences observed at W24 and W48. Adherence monitoring at W24, W48, and W96 revealed no impact on the differences observed between the two groups.
DynaM-O is the unique study analyzing the HAART responses in HIV-1/O infected patients compared to HIV-1/M patients. Data at W96 showed good efficacy of the regimens in both groups, but with a higher rate of achievement of the virological response in HIV-1/O infected patients. In contrast, the CD4 restoration was lower in HIV-1/O than that observed for HIV-1/M patients. These data indicate that group O infected patients should be successfully treated by treatment excluding NNRTI. Moreover, studying the mechanisms underlying these differences in response to HAART between these highly divergent HIV-1 strains are of importance in our understanding of the HIV natural history.